Extra-Large Pore Mesoporous Silica Nanoparticles Enabling Co-Delivery of High Amounts of Protein Antigen and Toll-like Receptor 9 Agonist for Enhanced Cancer Vaccine Efficacy.
Extra-Large Pore Mesoporous Silica Nanoparticles Enabling Co-Delivery of High Amounts of Protein Antigen and Toll-like Receptor 9 Agonist for Enhanced Cancer Vaccine Efficacy.
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DOI：
10.1021/acscentsci.8b00035
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发表时间：
2018-04-25
影响因子：
18.2
通讯作者：
Kim J
中科院分区：
文献类型：
--
作者：
Cha BG;Jeong JH;Kim J
癌症疫苗旨在激发抗肿瘤适应性免疫反应来检测和消除肿瘤。然而，目前基于树突状细胞（DCs）的癌症疫苗存在一些局限性，这些局限性主要来自患者树突状细胞的体外培养。为了规避这些限制，需要使用携带抗原的材料直接激活和成熟宿主dc，而不需要从患者身上分离dc。在这项研究中，我们展示了特大孔介孔二氧化硅纳米颗粒（XL-MSNs）的合成，并通过将癌症抗原和危险信号传递给引流淋巴结中的宿主DCs，将其用作预防性癌症疫苗。与传统的小孔MSNs相比，大约25 nm的超大孔和额外的表面修饰使XL-MSNs的抗原蛋白和toll样受体9 （TLR9）激动剂的负载显著增加。体外研究表明，DCs的活化和抗原呈递增强，促炎细胞因子的分泌增加。体内研究表明，接种疫苗后，XL-MSNs可有效靶向引流淋巴结，诱导抗原特异性细胞毒性T淋巴细胞（ctl），并抑制肿瘤生长。此外，免疫后的无瘤小鼠在肿瘤再攻击后的肿瘤生长得到了显著的预防，这是由高水平的记忆T细胞支持的。这些发现表明，具有超大孔隙的介孔二氧化硅纳米颗粒可以作为癌症疫苗的一个有吸引力的平台。研制了基于超大孔径介孔二氧化硅纳米颗粒的癌症疫苗。疫苗接种后获得的强抗原特异性免疫应答，即使在肿瘤再次攻击后也能显著阻止肿瘤生长。
Cancer vaccine aims to invoke antitumor adaptive immune responses to detect and eliminate tumors. However, the current dendritic cells (DCs)-based cancer vaccines have several limitations that are mostly derived from the ex vivo culture of patient DCs. To circumvent the limitations, direct activation and maturation of host DCs using antigen-carrying materials, without the need for isolation of DCs from patients, are required. In this study, we demonstrate the synthesis of extra-large pore mesoporous silica nanoparticles (XL-MSNs) and their use as a prophylactic cancer vaccine through the delivery of cancer antigen and danger signal to host DCs in the draining lymph nodes. Extra-large pores of approximately 25 nm and additional surface modification of XL-MSNs resulted in significantly higher loading of antigen protein and toll-like receptor 9 (TLR9) agonist compared with conventional small-pore MSNs. In vitro study showed the enhanced activation and antigen presentation of DCs and increased secretion of proinflammatory cytokines. In vivo study demonstrated efficient targeting of XL-MSNs co-delivering antigen and TLR9 agonist to draining lymph nodes, induction of antigen-specific cytotoxic T lymphocytes (CTLs), and suppression of tumor growth after vaccination. Furthermore, significant prevention of tumor growth after tumor rechallenge of the vaccinated tumor-free mice resulted, which was supported by a high level of memory T cells. These findings suggest that mesoporous silica nanoparticles with extra-large pores can be used as an attractive platform for cancer vaccines. Cancer vaccine based on extra-large pore mesoporous silica nanoparticles was developed. The strong antigen-specific immune responses obtained after vaccination significantly prevented tumor growth even after tumor rechallenge.
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影响因子：
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作者：
Jähnisch H;Füssel S;Kiessling A;Wehner R;Zastrow S;Bachmann M;Rieber EP;Wirth MP;Schmitz M
通讯作者：
Schmitz M
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作者：
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通讯作者：
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